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We demonstrate that NNMT outcompetes leucine carboxyl methyl transferase 1 (LCMT1) for methyl transfer from principal methyl donor SAM in biological systems. Inhibiting NNMT increased the availability of methyl groups for LCMT1 to methylate PP2A, resulting in the inhibition of oncogenic serine/threonine kinases (STK).
Studies indicate that protein phosphatase methylesterase-1 (PME-1) negatively regulates protein phosphatase 2A (PP2A (show PPP2R4 Proteins)) activity by highly complex mechanisms.
Data suggest that discovery of more potent protein phosphatase methylesterase-1 (PME-1) inhibitors may be beneficial for the treatment of endometrial cancer.
LCMT1 (show LCMT1 Proteins)-PME-1 methylation equilibrium is critical for regulating mitotic spindle size and thereby proper cell division
this study suggests that the tightly linked regulatory loop comprised of the SIK2 (show SIK2 Proteins)-PP2A (show PPP2R4 Proteins) and CaMKI (show CAMK1 Proteins) and PME-1 networks may function in fine-tuning cell proliferation and stress response.
PPME1 could be an attractive therapeutic target for a subset of gastric cancer and lung cancer.
Data indicate that PP2A (show PPP2R4 Proteins) holoenzyme biogenesis and activity are controlled by five PP2A (show PPP2R4 Proteins) modulators, consisting of alpha4, PTPA (show PPP2R4 Proteins), LCMT1 (show LCMT1 Proteins), PME-1 and TIPRL1, which serve to prevent promiscuous phosphatase activity until the holoenzyme is completely assembled.
GSK-3beta can inhibit PP2A (show PPP2R4 Proteins) by increasing the inhibitory L309-demethylation involving upregulation of PME-1 and inhibition of PPMT1 (show LCMT1 Proteins)
Academic cross-fertilization by public screening yields a remarkable class of protein phosphatase methylesterase-1 inhibitors.
We propose that stabilization of this inactive, nuclear PP2A (show PPP2R4 Proteins) pool is a major in vivo function of PME-1.
protects protein phosphatase 2A from ubiquitin/proteasome degradation
PME-1 plays a critical role in differentiation of neuroblastoma (show ARHGEF16 Proteins) cells.
targeted disruption of the PME-1 gene causes perinatal lethality in mice, a phenotype that correlates with a virtually complete loss of the demethylated form of PP2A (show PPP2R2B Proteins) in the nervous system and peripheral tissues
This gene encodes a protein phosphatase methylesterase localized to the nucleus. The encoded protein acts on the protein phosphatase-2A catalytic subunit and supports the ERK pathway through dephosphorylation of regulatory proteins. It plays a role in malignant glioma progression. Alternative splicing results in multiple transcript variants.
protein phosphatase methylesterase-1
, protein phosphatase methylesterase 1
, phosphatase methylesterase 1